Activation of mutant RB or functional loss of RB and PTEN in the TRP orthotopic model mimicked the alterations observed in human GBM, and allowed us to examine the relative importance of inhibiting the PI3K and MAPK pathways in vitro and in vivo using drugs that are currently in clinical trials for the treatment of GBM (Bendell et al., 2012; LoRusso et al., 2010). Here, RB1 is linked to glioblastoma.